Nature Neuroscience6, 1208 - 1215 (2003)
Published online: 19 October 2003; | doi:10.1038/nn1143
Regulation of gene expression and cocaine reward by CREB and FosB
Colleen A McClung
& Eric J Nestler
The University of Texas Southwestern Medical Center, Department of Psychiatry and Center for Basic Neuroscience, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
FosB (a truncated form of FosB) and CREB (cAMP response element binding protein) are transcription factors induced in the brain's reward pathways after chronic exposure to drugs of abuse. However, their mechanisms of action and the genes they regulate remain unclear. Using microarray analysis in the nucleus accumbens of inducible transgenic mice, we found that CREB and a dominant-negative CREB have opposite effects on gene expression, as do prolonged expression of FosB and the activator protein-1 (AP-1) antagonist cJun. However, unlike CREB, short-term and prolonged FosB induction had opposing effects on gene expression. Gene expression induced by short-term FosB and by CREB was strikingly similar, and both reduced the rewarding effects of cocaine, whereas prolonged FosB expression increased drug reward. Gene expression after a short cocaine treatment was more dependent on CREB, whereas gene expression after a longer cocaine treatment became increasingly FosB dependent. These findings help define the molecular functions of CREB and FosB and identify clusters of genes that contribute to cocaine addiction.
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FosB
FosB (a truncated form of FosB) and CREB (cAMP response element binding protein) are transcription factors induced in the brain's reward pathways after chronic exposure to drugs of abuse. However, their mechanisms of action and the genes they regulate remain unclear. Using microarray analysis in the nucleus accumbens of inducible transgenic mice, we found that CREB and a dominant-negative CREB have opposite effects on gene expression, as do prolonged expression of 
FosB in the brain controls sensitivity to cocaine
in 
